Effect and safety of mivacurium chloride and succinylcholine for bronchoscopy: study protocol for a single-center, randomized, non-inferiority, and positive-controlled clinical trial

Abstract

Background

Succinylcholine is favored for its rapid onset and offset, but its use is limited by adverse effects. Mivacurium chloride, a non-depolarizing relaxant, offers a similar shorter duration and fewer cardiovascular effects, especially without worrying about muscle pain and hyperkalemia, making it a potential alternative in some short-time operations. This study aims to assess the non-inferiority of mivacurium chloride compared to succinylcholine in terms of muscle relaxation effect and safety during flexible bronchoscopy.

Methods

This is a prospective, single-center, randomized, assessor-blinded, positive-controlled trial. Participants scheduled for flexible bronchoscopy requiring muscle relaxation were randomly assigned to receive either mivacurium chloride or succinylcholine. The primary endpoint is the recovery rate of spontaneous breathing within 15 min after discontinuation of muscle relaxants. Other outcomes, including recovery time at different levels, hemodynamic changes, adverse events, and satisfaction from physicians and patients, are also collected.

Discussion

This study aims to compare the recovery effect of mivacurium chloride for muscle relaxation during bronchoscopy with succinylcholine, hypothesizing that mivacurium chloride is non-inferior in recovery time and superior in safety and comfort.

Trials registration

Chinese Clinical Trial Registry ChiCTR2400091276. Registered on 23 October 2024. ClinicalTrials.gov NCT06709066. Posted on 29 November 2024.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09463-3.

Administrative information

Title {1}	Effect and safety of mivacurium chloride and succinylcholine for bronchoscopy: study protocol for a single-center, randomized and positive-controlled clinical trial
Trial registration {2a and 2b}	Chinese Clinical Trial Registry, ChiCTR2400091276, Registered on 23 October, 2024. ClinicalTrials.gov NCT06709066
Protocol version {3}	30 August 2024, version 2.0
Funding {4}	None
Author details {5a}	Xiang Zhang, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610,041, China. zhangxiang2000@163.com Yongqing Xu, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610,041, China. xuyongqing0301@163.com Jie Li, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610, 041, China. Department of Anesthesiology, Meishan People's Hospital, Meishan 620,020, China. 18,808,214,771@163.com Yufan Xi, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610,041, China.1620837539@qq.com Zhao Xu, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610,041, China. davidxuzhao@gmail.com Peng Liang, Corresponding author. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610, 041, China. Day Surgery Center of General Practice Medical Center, West China Hospital, Sichuan University, Chengdu 610,041, China. liangpengwch@scu.edu.cn
Name and contact information for the trial sponsor {5b}	The trial sponsor is the West China Hospital of Sichuan University, Chengdu, China. Postal address: No.37 Guoxue Alley, Chengdu 610,041, Sichuan, China. Tel: + 862,885,423,592, Fax: 86–28–85,423,593
Role of sponsor {5c}	The trial sponsor has a regulatory role and will play a part in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication

Introduction

Background and rationale {6a}

Flexible bronchoscopy is a cornerstone diagnostic and interventional tool in modern respiratory medicine, offering direct visualization of the airways and enabling procedures such as biopsy, lavage, and suction [1]. This procedure allows physicians to insert a slender bronchoscope through the patient’s mouth, nose, or tracheotomy site, enabling direct visualization of abnormalities in the trachea, bronchi, and their branches. However, since bronchoscopy involves accessing highly sensitive airway regions, it often triggers discomfort and stress responses in patients, such as coughing, breath-holding, and elevated heart rates [2]. These reactions not only hinder the smooth progression of the procedure but may also cause additional pain and potential harm to the patient. With the growing emphasis on patient-centered care, painless bronchoscopy is frequently performed under general anesthesia with laryngeal mask airway (LMA)-positive ventilation, enhancing both patient comfort and diagnostic accuracy [3].

In clinical practice, anesthetic agents play a crucial role in facilitating procedures. The selection of an appropriate anesthetic requires a comprehensive evaluation of factors such as onset time, duration of action, and impact on the cardiovascular system. Flexible bronchoscopy, a satisfied procedure demanding both effective muscle relaxation and rapid postoperative recovery, places significant demands on anesthetic management, particularly regarding the choice of muscle relaxants. Depolarizing muscle relaxants, such as succinylcholine, are favored for their rapid onset, strong muscle relaxation, and quick recovery, which is chosen for painless bronchoscopy in most of medical centers. However, their clinical use has diminished due to a higher incidence of adverse postoperative effects, including fasciculation, myalgia, and hyperkalemia [4, 5]. To mitigate stress responses and improve the safety and comfort of bronchoscopy, particularly for elderly patients and those with cardiovascular comorbidities, it is essential to choose a muscle relaxant that balances efficacy with safety.

Mivacurium chloride, a novel non-depolarizing muscle relaxant, has gained increasing attention in clinical anesthesia in recent years. Its primary characteristics include rapid onset, short duration of action, and quick recovery. In comparison, traditional depolarizing muscle relaxants like succinylcholine provide effective muscle relaxation but are associated with a higher incidence of adverse postoperative effects. In addition to the adverse effects such as hyperkalemia, the most common complaint from patients is muscle pain after surgery, which is associated with muscle contraction by succinylcholine. Therefore, mivacurium chloride may present significant advantages for both short-duration procedures and fewer adverse effects.

Objectives {7}

Evidence remains limited regarding the use of mivacurium chloride for painless flexible bronchoscopy. The primary objective of this trial is to determine whether mivacurium chloride is non-inferior to succinylcholine with respect to timely recovery, defined as recovery of spontaneous breathing within 15 min after discontinuation of the muscle relaxant. The secondary objectives are to compare procedural conditions and safety profiles between groups, including intraoperative events reflecting operating conditions.

Trial design {8}

This prospective, single-center, assessor-blinded, non-inferiority randomized clinical trial aims to evaluate the efficacy of mivacurium chloride compared with succinylcholine in painless flexible bronchoscopy. This is a two-arm, parallel-group trial with a 1:1 allocation ratio. The non-inferiority framework will be applied to assess whether mivacurium chloride is non-inferior to succinylcholine in terms of recovery time. Data will be collected on basic demographics, vital signs during the procedure, recovery metrics (including spontaneous breathing, consciousness, and laryngeal mask airway removal), and adverse events at each clinical visit.

Patient and public involvement in the design of this trial was not performed. However, we acknowledge the growing importance of patient-centered care and recognize the value of patient and public involvement in future research. For future trials, we plan to actively engage patient advocacy groups and public representatives in the design and implementation phases to align the research with patient priorities.

Methods: participants, interventions and outcomes

Study setting {9}

This study is being conducted at West China Hospital of Sichuan University. Ethical approval for the study has been obtained from the hospital’s Ethics Committee, ensuring that all aspects of the trial adhere to ethical standards. Prior to enrollment, all participants will provide written informed consent, affirming their voluntary participation and understanding of the study’s purpose, procedures, potential risks, and benefits. The study is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines to ensure rigorous methodological quality and transparency (Additional file 1).

Eligibility criteria {10}

Inclusion criteria

1. Patients scheduled for flexible bronchoscopy requiring the use of muscle relaxants.

2. Aged 18 years

3. Classified as American Society of Anesthesiologists (ASA) status I to III.

4. Willing to participate voluntarily, with signed informed consent.

Exclusion criteria

1. Known allergies to any study-related drugs.

2. Severe organic diseases affecting the brain, heart, lungs, liver, or kidneys.

3. Conditions such as intracranial hypertension, asthma, cataracts, or glaucoma.

4. Neuromuscular disorders, including myasthenia gravis, myasthenic syndrome, severe cholinesterase deficiency, upper motor neuron injuries, or diseases affecting neuromuscular blocking agents.

5. History of or current use of drugs affecting neuromuscular transmission before surgery.

6. Pregnancy or breastfeeding women.

7. Major burns, acid–base imbalance, or electrolyte disturbances within the past 6 months

8. Known or suspected homozygous atypical plasma cholinesterase gene carriers.

Eligibility for study centres and intervention performers

Not applicable.

Who will take informed consent? {26a}

During preoperative visits, trained investigators will explain the purpose, methods, risks, and benefits of the study to potential participants. Participants will be given sufficient time to review the consent form, ask any questions, and ensure they fully understand the study before providing consent. Written informed consent will be obtained from participants before any study-related procedures are performed.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

As part of the study, participants' data will be collected during the intervention and anesthesia regimen. Participants will also consent to the collection and use of venous blood samples for study-related safety assessments, as specified in the protocol (Section "Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}"), including measurement of serum potassium and plasma creatine kinase-MB at baseline and 24 h post-procedure. All data and specimens will be coded using unique study identifiers to protect privacy; the linking key will be stored separately and accessible only to authorized personnel. Data will be handled in strict confidence and reported only in aggregated form.

Interventions

Explanation for the choice of comparators {6b}

Succinylcholine is a commonly used depolarizing muscle relaxant known for its rapid onset and offset, making it suitable for short-duration procedures like flexible bronchoscopy. However, its use is limited by adverse effects, including myalgia and hyperkalemia. Mivacurium chloride, a non-depolarizing muscle relaxant, offers a similar rapid onset but with fewer cardiovascular side effects. Unlike succinylcholine, mivacurium chloride avoids the muscle pain and hyperkalemia, making it a potential alternative, especially for patients with contraindications to succinylcholine or those requiring a safer muscle relaxant for brief procedures.

Intervention description {11a}

No premedication will be administered before entering the operating room. Baseline data will be gathered prior to anesthesia, including age, gender, height, weight, allergy history, medical history, diagnosis, type of operation, ASA physical status, vital signs (blood pressure and heart rate), complete blood count (red blood cells, white blood cells, platelets, hemoglobin), blood biochemistry (creatine kinase-MB (CK-MB) and potassium levels), and an electrocardiogram (ECG). All patients are placed in the supine position with ECG, NBP, SpO₂, and bispectral index (BIS) monitoring. After preoxygenation with a face mask at 6 L/min for 3 min, sufentanil 0.15 mcg/kg is administered intravenously over 10 ± 5 s. One minute later, ciprofol 0.4 mg/kg is administered intravenously over 20 ± 5 s. Following ciprofol administration, the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score is evaluated every 30 s (Table 1) [6, 7]. Once the MOAA/S score reaches 0 or 1, patients in the study group receive an intravenous bolus of mivacurium chloride 0.14 mg/kg over 10 ± 5 s, followed by continuous infusion at 0.5 mg/kg/h. Patients in the control group receive an intravenous bolus of succinylcholine 1 mg/kg over 10 ± 5 s, followed by continuous infusion at 5 mg/kg/h. These dosages were chosen based on both published pharmacologic data and pilot observations at our institution, demonstrating adequate depth of relaxation and optimal surgical conditions during bronchoscopy [8]. Because succinylcholine produces a depolarizing block without sequential fade, quantitative neuromuscular monitoring would not provide a meaningful comparison with the non-depolarizing agent mivacurium and was therefore not performed. Two minutes later, a laryngeal mask is inserted, and mechanical ventilation is initiated. Volume-controlled mode ventilation is performed with 8 ml/kg tidal volume and end-tidal carbon dioxide (ETCO₂) maintained at 30–40 mmHg. The flexible bronchoscopy procedure begins thereafter. Drug infusions are discontinued upon the removal of the bronchoscope from the vocal cords. The LMA is removed when the patient demonstrated signs of awakening, such as spontaneous eye opening, purposeful extremity movement without physical stimulation, and response to verbal commands, along with achieving a tidal volume > 5 mL/kg and a respiratory rate > 12 breaths per minute [9]. Oxygen is administered via nasal cannula at 3 L/min. Patients are then transferred to the recovery room for further observation.

Table 1.

Modified observer’s assessment of alertness/sedation score

Score	Responsiveness
6	Agitated
5	Responds readily to name spoken in normal tone
4	Lethargic response to name spoken in normal tone
3	Responds only after name is called loudly and/or repeatedly
2	Responds only after mild prodding or shaking
1	Does not respond to mild prodding or shaking
0	Does not respond to deep stimulus

Criteria for discontinuing or modifying allocated interventions {11b}

Adverse events, whether or not related to the experimental treatment, are considered undesirable and are recorded if spontaneously reported by the patient or observed by the investigators. Serious adverse events are defined as any untoward occurrence that causes death, is life-threatening, requires prolonged hospitalization, or results in significant persistent disability. The safety endpoints include the incidence and severity of all adverse events during the study period, as well as specific events such as hypotension (systolic blood pressure drop > 20% from baseline), tachycardia (heart rate increase > 20% from baseline), bradycardia, skin flushing, acute bronchospasm immediately following drug administration, erythema/urticaria, body movement, and severe cardiovascular events (malignant arrhythmias, acute myocardial ischemia). Additional safety assessments will include the use of vasoactive drugs (type and total dosage), delayed neuromuscular recovery (failure to resume spontaneous breathing 30 min after drug cessation), postoperative muscle pain (severity and impact on mobility), postoperative plasma CK-MB levels, myoglobinuria screening through urine color assessment (with urinalysis if abnormalities are found), and other adverse events. These events will be closely monitored throughout the study, and appropriate interventions will be implemented as needed to ensure participant safety.

Strategies to improve adherence to interventions {11c}

Not applicable. As all interventions in this study are administered during anesthesia and are not dependent on patient cooperation, adherence to intervention protocols will be ensured through strict procedural oversight.

Relevant concomitant care permitted or prohibited during the trial {11d}

Standard perioperative care, including appropriate fluid management and monitoring, will be provided. Anesthetic agents mentioned in protocols can be used for induction and maintenance. Additional sedatives or analgesics outside the protocol may be administered only if required for patient safety. The concurrent use of any other neuromuscular blocking agents or drugs known to interfere with muscle relaxation is prohibited during the trial.

Provisions for post-trial care {30}

Participants will be monitored in the recovery room after the procedure for any immediate adverse effects of the muscle relaxants. Post-procedure follow-up visits will be conducted at 6 and 24 h to monitor recovery and report any adverse events. If a participant suffers harm due to trial participation, medical care will be provided free of charge.

Outcomes {12}

The primary endpoint of the study is the rate of spontaneous breathing recovery within 15 min after discontinuation of mivacurium chloride and succinylcholine.

The secondary endpoints include the comparison of mean recovery times between the mivacurium chloride and succinylcholine groups for spontaneous breathing and consciousness, both assessed up to 15 min post-procedure. Spontaneous breathing recovery is defined as achieving a tidal volume of 5 ml/kg and a respiratory rate of 12 breaths per minute, while consciousness recovery is defined as the ability to open eyes upon verbal command or when called by name. The time to remove the LMA will also be compared between the two groups, assessed within 15 min post-procedure. Cardiovascular parameters, including mean blood pressure, heart rate, BIS value, and SpO₂, will be recorded simultaneously at key stages: pre-induction, during induction (at 1-min intervals until LMA insertion), and post-induction (every 3 min after LMA insertion, surgery start, surgery end, and LMA removal). The mean values for these parameters will be calculated for each stage. Exploratory endpoints will assess the level of smoothness during bronchoscopy, including the incidence of intraoperative coughing and glottis opening during the procedure. Satisfaction ratings from both the anesthesiologist and the patient are also collected.

Participant timeline {13}

Participants will be screened from 7 days to the day of surgery for eligibility, informed consent, and baseline assessments. On the day of surgery, following baseline evaluations and anesthesia induction, participants will be randomized to receive either mivacurium chloride or succinylcholine before undergoing flexible bronchoscopy. Postoperative recovery, including assessments of spontaneous breathing, consciousness, LMA removal, adverse events, and satisfaction, will be evaluated at 6 and 24 h after surgery. The complete schedule of enrollment, interventions, and assessments is detailed in Table 2 and Fig. 1.

Table 2.

Participant timeline

Study period
	Enrollment	Allocation	Intervention	Post-intervention
Timepoint	− 7 to 0 days	− 7 to 0 days	Surgery day	6 h post-surgery	24 h post-surgery
Enrollment
Eligibility screen	X
Informed consent	X
Inclusion/exclusion criteria	X
Medical history & demographics	X
Physical examination, vital signs	X
Laboratory tests (blood routine, biochemistry)	X
12-lead ECG or cardiac monitoring	X
Surgical information	X
Allocation		X
Interventions
Administration of sufentanil + ciprofol			X
Study drug (mivacurium chloride or succinylcholine)			X
Laryngeal mask airway insertion, mechanical ventilation			X
Flexible bronchoscopy procedure			X
Assessments
Vital signs			X
BIS			X
MOAA/S score			X
Primary outcome assessment
Spontaneous breathing recovery			X
Secondary outcome assessments
Recovery times for consciousness and LMA removal			X
Exploratory assessments
Intraoperative events (e.g., incidence of coughing, glottis opening)			X
Postoperative assessments
Adverse events monitoring				X	X
Concomitant medications recording				X	X
Satisfaction evaluation (physicians & patients)				X	X

ECG electrocardiogram, MOAA/S score Modified Observer's Assessment of Alertness/Sedation score, BIS bispectral index, LMA laryngeal mask airway

Fig. 1.

The flow chart of the present trial

Sample size {14}

The PASS 2021, v21.0.3 (NCSS, LLC, USA), software is used to calculate the sample size based on the primary endpoint. At a dose of 1 mg/kg, succinylcholine produces rapid onset and short duration of neuromuscular block; recovery of neuromuscular function is typically achieved within 10–13 min to T1 90% [10, 11]. In our center, succinylcholine is routinely used for painless flexible bronchoscopy under a standardized ciprofol–sufentanil anesthetic regimen. Based on a pilot study, approximately 98% of patients regain spontaneous breathing within 15 min after discontinuation of succinylcholine. Therefore, the 15-min spontaneous-breathing recovery rate was selected as the primary endpoint, reflecting a clinically meaningful recovery target for short bronchoscopy procedures.

For sample size planning, we adopted a conservative assumption that the 15-min spontaneous-breathing recovery rate with mivacurium would be approximately 95%, slightly lower than that observed with succinylcholine in our routine practice. This assumption was chosen to avoid an overly optimistic estimate in a non-inferiority design and is supported by the established short-acting profile of mivacurium as well as our institutional pilot experience indicating that the selected dosing regimen provides satisfactory conditions for bronchoscopy while allowing rapid recovery [12].

The sample size in each group should be 108 to achieve a power of 80% at a one-sided significance level of 0.025, with a non-inferiority margin of 10%. The formal hypotheses were specified as follows: H_₀: pₘ−pₛ ≤−Δ (the recovery rate for mivacurium is inferior to succinylcholine by more than 10%) and H₁: pₘ−pₛ >−Δ (mivacurium is non-inferior to succinylcholine). The non-inferiority margin of 10% (absolute difference) was determined based on clinical relevance and consistency with previous non-inferiority anesthesia trials. Similar studies, which compared mivacurium and rocuronium in rapid sequence induction, also adopted a 10% margin [12]. A drop-out rate of 10% was adopted to ensure that the study remains adequately powered in the event of unexpected patient withdrawal or incomplete follow-up, even in a controlled perioperative setting. Similar sample size calculations in perioperative clinical trials have anticipated a drop-out rate of 10% when estimating required sample sizes to compensate for potential loss to follow-up in surgical patients [13]. Considering a drop-out rate of 10%, the final required sample size is 120 in each group, leading to a total of 240 subjects for the study.

Recruitment {15}

Recruitment will be conducted at West China Hospital, and participants will be informed about the trial through clinic visits. The study team will ensure that the eligibility criteria are strictly followed to enroll the target sample size. All patients aged 18 to 60, scheduled for flexible bronchoscopy requiring muscle relaxation, and classified as ASA status I to III will be screened daily by the investigator. Verbal and written information regarding the trial will be provided if they meet all inclusion criteria and have no exclusion criteria. The recruitment of patients is ongoing. As a high-volume center, we will be able to identify eligible patients and recruit the required sample size.

Assignment of interventions: allocation

Sequence generation {16a}

All consenting patients meeting the inclusion criteria will be randomly assigned to either the mivacurium chloride group or the succinylcholine group. Randomization will be performed using a computer-generated table and implemented with a variable block randomization method in a 1:1 ratio to ensure equal distribution of patients between the groups.

Concealment mechanism {16b}

The allocation will be concealed using opaque, sealed envelopes. Each envelope will contain a concealed allocation number corresponding to the randomization list.

Implementation {16c}

The list will be generated and securely maintained by an individual not involved in the study, ensuring blinding in the operating room. The number of envelopes will match the number of patients eligible for randomization, with each envelope sequentially numbered according to the generated list.

Assignment of interventions: blinding

Who will be blinded {17a}

Double blinding will not be feasible due to the muscle fasciculations caused by succinylcholine; however, outcome assessors will remain blinded to the group assignments [14].

Procedure for unblinding if needed {17b}

Unblinding is strictly limited to situations where immediate knowledge of a participant’s allocated intervention is essential for patient safety, such as in the event of a serious adverse event requiring urgent clinical decision-making. In such cases, the study investigator will contact the independent individual responsible for maintaining the randomization list and sealed allocation envelopes. This individual will then reveal the participant’s allocated treatment to the necessary clinical staff. Every instance of unblinding will be documented in detail, including the reason, date, and time of unblinding, and will be reported to the study monitoring committee.

Data collection and management

Plans for assessment and collection of outcomes {18a}

Outcome, baseline, and other trial data will be collected using standardized case report forms (CRF) that have been pretested for accuracy and clarity. Data collection includes basic demographics, vital signs during the procedure, recovery metrics (spontaneous breathing, consciousness, and laryngeal mask airway removal), laboratory test results (e.g., complete blood count, blood biochemistry, 12-lead ECG), and adverse events. Measurements will be performed by trained study personnel using validated instruments and standardized operating procedures. Duplicate measurements will be taken where applicable to ensure data quality, and assessors receive regular training to maintain consistency and reliability throughout the study.

Plans to promote participant retention and complete follow-up {18b}

To enhance participant retention and ensure complete follow-up, clear communication about the study schedule will be provided at enrollment. Follow-up visits are scheduled for the day of surgery, as well as at 6 and 24 h post-surgery. In cases where participants discontinue the intervention or deviate from the protocol, the study team will actively contact them (via telephone or in-person) to collect all available outcome data. A detailed log of any discontinuations or protocol deviations will be maintained, and reasons for such events will be recorded to facilitate accurate interpretation of the study results.

Data management {19}

All study data will initially be recorded on paper case report forms using standardized templates and guidelines. Once completed, these paper records will be stored in a secure, locked filing cabinet at the study site. Trained study staff will then enter the data into a dedicated electronic study database, ensuring a secure and direct transfer to the study office without intermediary steps. The principal investigators (PIs) will routinely review both the paper CRFs and the electronic database to verify that the data are complete, accurate, and in compliance with the study protocol. Regular quality checks and validation procedures, including detection of duplicate records and verification of value ranges, will be performed. All research personnel will receive comprehensive training on data collection, entry procedures, and protocol adherence. Both the paper and electronic records will be maintained for a minimum of 3 years after the trial concludes, and the final report is published.

Confidentiality {27}

To safeguard participant confidentiality, all collected data will be de-identified by assigning unique study codes. The key linking these codes to individual identities will be stored separately in a secure location accessible only to authorized personnel. All documents containing sensitive information will be kept under lock and key, and data will be reported only in aggregate form to prevent the identification of individual participants.

Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

Venous blood samples will be collected at pre-procedure and at 24 h post-procedure to measure serum potassium and plasma CK-MB as safety-related biomarkers, given the known risk of hyperkalemia and muscle injury associated with succinylcholine. All measurements will be performed using the hospital’s routine clinical laboratory assays. No genetic testing or molecular analyses are planned in this trial, and specimens will not be stored for future genetic or ancillary analyses unless additional consent is obtained. All samples will be labeled with unique study codes and handled according to institutional procedures to maintain confidentiality.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

For the primary endpoint (recovery of spontaneous breathing within 15 min), the treatment effect will be expressed as the risk difference, defined as pₘ−pₛ (mivacurium minus succinylcholine). Non-inferiority will be assessed against the prespecified margin Δ = 10% (absolute difference) using a one-sided 97.5% confidence interval. Non-inferiority will be concluded if the lower bound of the confidence interval is greater than −10%. This evaluation will be performed in both the intention-to-treat (ITT) and per-protocol (PP) populations, and non-inferiority will be declared only if both analyses support non-inferiority. As a supportive measure, the primary endpoint will also be summarized using relative risk (RR) with corresponding confidence intervals. Baseline characteristics will be summarized using descriptive statistics, including mean, standard deviation (SD), median, minimum, maximum, and interquartile range for continuous variables, and counts and percentages for categorical variables.

Secondary outcomes will be analyzed primarily on a superiority basis using two-sided tests with α = 0.05. Continuous outcomes will be compared using independent-samples t-test or Mann–Whitney U-test as appropriate, and categorical outcomes will be compared using χ² test or Fisher’s exact test. Effect estimates with confidence intervals will be reported. Multivariable regression will be applied to adjust for potential confounding variables such as age, baseline comorbidities, and vital signs.

Statistical significance will be set at α = 0.05, and a p ≤ 0.05 will be considered statistically significant. All analyses will be conducted using SPSS software (SPSS 26.0, Chicago, IL, USA).

Interim analyses {21b}

Interim analysis is planned to be conducted when 50% of the participants have completed the trial. This interim analysis will focus on key safety and efficacy data to ensure the trial is proceeding as expected. Since this is a low-risk intervention, the PI will conduct the interim analysis and review the data at that stage. If any significant safety concerns arise, the PI will consult with the Ethics Committee to determine whether the trial should be stopped early. Pre-specified stopping rules include severe adverse events, such as those requiring hospitalization or unexpected risks to participants’ safety.

Methods for additional analyses (e.g. subgroup analyses) {20b}

Subgroup analyses will be conducted based on age, gender, and key baseline characteristics. Additionally, exploratory analyses will evaluate outcomes across various risk profiles and procedural factors to further elucidate the treatment effect.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

Data is first recorded on paper case report forms using standardized templates and subsequently entered into a secure electronic database by trained study staff. Automated validation checks and manual reviews are then conducted to ensure data completeness and consistency. Any identified discrepancies, out-of-range values, or missing key information will be flagged and referred to the study investigators for clarification. All corrections will be logged in an audit trail, and a final audit comparing the electronic records with the original paper forms will be performed prior to database closure. For missing data, we will first examine the extent and pattern of missingness. If missing data are determined to be non-negligible, a multiple imputation method will be applied under the assumption that data are missing at random. This imputation approach will incorporate all relevant baseline and outcome variables to generate robust estimates, and sensitivity analyses comparing imputed data with complete-case analyses will be conducted to ensure the robustness of the study findings.

Plans to give access to the full protocol, participant level-data and statistical code {31c}

The full protocol, de-identified participant-level dataset, and statistical code will be made available by the corresponding author upon reasonable request, in accordance with institutional policies and ethical guidelines.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {5d}

The study is managed by a central team at West China Hospital of Sichuan University, which includes experienced anesthesiologists and data analysts responsible for the day-to-day execution and data quality assurance. The coordinating center for this study is based at West China Hospital and is responsible for overseeing the day-to-day management of the trial. It consists of the PI, data manager, research assistants, and ethics committee representatives. The coordinating center ensures that all aspects of the trial, including participant recruitment, data collection, and adherence to the study protocol, are effectively managed, and that the trial complies with regulatory and ethical standards. This internal team convenes virtually on a weekly basis to review study progress, address operational challenges, and ensure adherence to the protocol. There is no separate trial steering committee or external stakeholder group; all oversight responsibilities are integrated within the coordinating center.

Composition of the data monitoring committee, its role and reporting structure {21a}

Since this is considered a low-risk intervention, a formal data monitoring committee has not been established. Instead, interim analysis will be conducted by the PI, and any significant findings will be reviewed with the ethics committee.

Adverse event reporting and harms {22}

Adverse events related to the use of muscle relaxants in this study will be closely monitored throughout the trial. Potential adverse events include a significant drop in systolic blood pressure greater than 20% from baseline, an increase in heart rate exceeding 20% from baseline, and episodes of bradycardia that could compromise cardiovascular stability. Neuromuscular adverse events, such as delayed recovery of spontaneous breathing and postoperative muscle pain, will also be documented. In addition, acute bronchospasm and other unexpected cardiovascular events will be recorded. All adverse events will be promptly managed according to the study protocol, with detailed documentation of their severity, duration, and relationship to the intervention. Serious adverse events will be reported immediately to the Institutional Review Board, and participants experiencing any adverse event will receive appropriate medical care and be followed until the event is fully resolved.

Frequency and plans for auditing trial conduct {23}

The trial will undergo 6-monthly reviews conducted by the Ethics Committee at West China Hospital to ensure compliance with ethical standards and participant safety. Additionally, the PI will perform biweekly checks on the study data and procedural adherence to promptly identify any deviations from the protocols. Any findings from these checks will be discussed with the study team, and corrective actions will be implemented immediately to ensure that the trial is conducted according to the protocol.

Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}

Any substantial amendments to the protocol, like modifications to eligibility criteria, outcome measures, or statistical analysis plans, will be formally documented and submitted to the Ethics Committee for review and approval before implementation. Once approved, these amendments will first be documented and submitted to the sponsor for approval. Once approval is obtained, the PI will notify the relevant study personnel and ensure the revised protocol is added to the Investigator Site File. Any protocol deviations will be fully documented using a breach report form, and the protocol will be updated in the clinical trial registry to reflect the changes.

Dissemination plans {31a}

Upon completion of the study, the primary outcomes will be submitted for publication in a reputable, peer-reviewed journal and presented at relevant national and international conferences. To foster transparency and support future research, the full study protocol, along with de-identified participant-level data and statistical analysis code, will be made available to interested researchers upon reasonable request, in compliance with ethical guidelines and institutional policies.

Discussion

This study aims to assess the non-inferiority of mivacurium chloride compared to succinylcholine in terms of muscle relaxation recovery and safety during bronchoscopy procedures. Both agents are commonly used in clinical practice but have distinct pharmacokinetic profiles. We hypothesize that their recovery times will not differ significantly, supporting the use of mivacurium chloride as a viable alternative to succinylcholine in scenarios where rapid recovery is required.

Succinylcholine is preferred for its quick onset and offset, making it ideal for short-duration procedures. However, mivacurium chloride, a non-depolarizing muscle relaxant, may be a better option for patients with contraindications to depolarizing agents, such as those with a history of malignant hyperthermia, hyperkalemia, etc. This study aims to determine whether mivacurium chloride can provide comparable recovery times without significantly prolonging recovery, thereby offering clinicians an alternative in situations where succinylcholine may not be appropriate or available.

Regarding safety, both agents are generally well-tolerated, though differences in adverse events, such as muscle pain, hypotension, or bradycardia, may influence the choice between them. This study will assess these adverse events to provide further insight into which agent may be better tolerated in the context of bronchoscopy.

A key strength of this study is its randomized controlled trial design, which minimizes bias and enhances the reliability of our findings. The inclusion of both primary and secondary outcomes allows for a comprehensive assessment of both efficacy and safety. Furthermore, the relatively large sample size strengthens the statistical power of the results.

However, there are several limitations to consider. First, the study was conducted at a single center, which may limit the external validity of the results. Multicenter studies would help confirm the findings and expand their applicability across diverse clinical environments. Additionally, while we employed intention-to-treat analysis, the 24-h postoperative follow-up may not fully capture the long-term effects of these muscle relaxants. Future studies with extended follow-up periods are necessary to assess the long-term safety and efficacy of mivacurium chloride and succinylcholine. Another notable limitation is the lack of train-of-four (TOF) monitoring, which could have provided more precise measurements of neuromuscular blockade depth. However, due to the different pharmacodynamic profiles of depolarizing and non-depolarizing agents, interpreting TOF results in this context would have been challenging, and thus, we excluded it from our analysis. Future research could examine the relationship between muscle relaxation depth and recovery more thoroughly, especially in longer procedures or patients with specific comorbidities.

Trial status

The current protocol version is 2.0 (30 August 2024). Recruitment started in October 2024 and was completed in December 2025. Follow-up for the protocol-defined postoperative assessments has been completed, and data analysis is ongoing at the time of manuscript revision.

Abbreviations

LMA

Laryngeal mask airway

SPIRIT

Standard Protocol Items: Recommendations for Interventional Trials

ASA

American Society of Anesthesiologists

CK-MB

Creatine Kinase-MB

ECG

Electrocardiogram

BIS

Bispectral index

MOAA/S

Modified Observer's Assessment of Alertness/Sedation

ETCO₂

End-tidal carbon dioxide

CRF

Case report forms

SD

Standard deviation

TOF

Train-of-Four

Authors’ contributions {31b}

Peng Liang is the chief investigator, he conceived the study, led the proposal and protocol development. Xiang Zhang and Yongqing Xu contributed to study design and to development of the proposal. Jie Li is the lead trial methodologist. Yufan Xi drafted the manuscript. Zhao Xu critically revised the manuscript. All authors read and approved the final manuscript.

Funding {4}

None. This study received no external funding. Study personnel were supported through routine salaries provided by West China Hospital, Sichuan University.

Data availability {29}

Any data required to support the protocol can be supplied on request.

Declarations

Ethics approval and consent to participate {24}

Informed consent will be obtained from all participants, or their legal representatives, in writing prior to inclusion in the trial. The study protocol has been approved by the Medical Ethics Committee of the West China Hospital, Sichuan University, on September 20, 2024 (Approval No. 1625). This study is registered with the Chinese Clinical Trial Registry (ChiCTR2400091276, registered on 23 October 2024) and with ClinicalTrials.gov (NCT06709066).

Consent for publication {32}

Not applicable. No identifying images or personal details of participants are included in this protocol or will be included in the trial results. A model consent form is available from the corresponding author upon request.

Competing interests {28}

The authors declare that they have no competing interests.